Process for preparing 2-aminobenzothiazole and its n-alkyl substitution products from 2-mercaptobenzothiazole

ABSTRACT

2-AMINOBENZOTHIAZOLE AND ITS N-ALKYL SUBSTITUTED PRODUCTS ARE PREPARED REACTING 2-MERCAPTOBENZOTHIAZOLE WITH AN AMINE AND SULFUR DIOXIDE INTHHE PRESENCE OF A METAL OXIDE, HYDROXIDE OR SALT CATALYST AT ELEVATED TEMPERATURE AND PRESSURE.

United States Patent 3,781,297 PROCESS FOR PREPARING Z-AMINOBENZOTHIA- ZOLE AND ITS N-ALKYL SUBSTITUTION PROD- UCTS FROM Z-MERCAPTOBENZOTHIAZOLE Dieter Pawellelr, Leverkusen, and Karlfried Wedemeyer,

Cologne-Stammheim, Germany, assignors to Bayer Aktiengesellschaft, Leverkusen, Germany No Drawing. Filed Dec. 2, 1971, Ser. No. 204,313 Claims priority, application Germany, Dec. 8, 1970, P 20 60 197.2 Int. Cl. C07d 91/46 US. Cl. 260305 6 Claims ABSTRACT OF THE DISCLOSURE Z-aminobenzothiazole and its N-alkyl substituted products are prepared reacting Z-mercaptobenzothiazole with an amine and sulfur dioxide inthhe presence of a metal oxide, hydroxide or salt catalyst at elevated temperature and pressure.

BACKGROUND This invention relates to a greatly improved process for the preparation of Z-aminobenzothiazole and it N-alkyl substitution products.

SUMMARY It has been found that 2-aminobenzothiazole and its N-alkyl substitution products can be easily obtained in excellent yields and in a high degree of purity by reacting Z-mercaptobenzothiazole, if desired in the form of its salts, in an aqueous medium with at least the stoichiometrically required quantity of an amine of the following formula wherein R and R which may be the same or different are hydrogen atoms or lower alkyl radicals (preferably C -C which together may be the constituents of a 5-, 6- or 7-membered ring system, in which in the case of a 6- membered ring this may contain an oxygen or sulphur atom as an additional hetero atom or a nitrogen atom which is substituted with a lower alkyl radical (prefery C1-C6),

and with at least the stoichiometrically required quantity of sulphur dioxide in the presence of an alkali metal, e.g. lithium, sodium, potassium or alkaline earth metal, e.g. magnesium, calcium or of a metal of the first or second sub-group of the periodic system, e.g. zinc in the form of oxides, hydroxides or the salt of acids which are Weaker than sulphurous acid, the reaction being carried out at a temperature range of from 80 C. to 240 C. at elevated pressure.

DESCRIPTION 3,781,297 Patented Dec. 25, 1973 Anorganische Chemie, Friedrich Vieweg u. Sohn, Brannschweig, 12th ed. (1948) zinc salts being preferred.

Salts of acids which are weaker than sulphurous acid should be understood to mean those which have a p;;- value greater than 1.92. The preferred salts are those of lower aliphatic carboxylic acids (containing 1 to 4 carbon atoms, preferably acetic acid) and those of carbonic acid and of Z-mercaptobenzothiazole.

The preparation of, for example, Z-methylaminobenzothiazole by the reaction of Z-mercaptobenzothiazole and methylamine in the presence of sulphur dioxide in aqueous solution has been described for the first and only time in the literature by I. Ubaldini and A. Fiorenza (G. 76, 216 (1946); C. A., 41, 960-1 (1947)). The reaction is carried out with a molar ratio of 1:52:35 in a sealed thick-walled glass tube at C. and the desired 2- methylaminobenzothiazole is isolated after 4 hours in a 25% yield. With a 47% conversion of Z-mercaptobenzothiazole, the yield is calculated to be 54% of the theory. When this method was re-tested by us it was found that quantitative conversion can be achieved by this method only after a reaction time of 24 hours, the unreacted 2- mercaptobenzothiazole cannot be readily isolated and reused in the reaction. Separation from the sulphur which is also precipitated during the isolation of not reacted starting material can only be achieved by repeated re-dissolving in sodium hydroxide solution which leads to considerable loss of product. Even then the product still contains a considerable quantity (approximately 10%) of elementary sulphur. The amount of time which has to be expended, and the fact that conversion is not quantitative, make it clear that the synthesis of for example 2-methylamino-benzothiazole could become technically important only if substantially complete conversion of the Z-mercaptobenzothiazole were achieved and this cannot be obtained by the known method.

It must therefore be regarded as expressivly surprising that the catalysts used according to the invention enable Z-aminobenzothiazole and its N-alkyl substitution products to be easily produced on a technical scale. The process of the invention may, of course, be carried out not only with Z-mercaptobenzothiazole as starting material but also by preparing instead the alkali metal salts, the alkaline earth metal salt or the sub-group metal salt of Z-mercaptobenzothiazole in a preliminary reaction and then reacting such a salt with the above described amines or ammonia and sulphur dioxide in an aqueous medium.

The molar ratios of the reactants may be varied to a considerable extent in the process of the invention. The molar ratio of 2-mercaptobenzothiazole to sulphur dioxide should not be higher than 1. An excess of sulphur dioxide in no way impairs the ease with which the process can be carried out. Preferably, 2 mols of sulphur dioxide are used per mol of Z-mercaptobenzothiazole.

The ratio of Z-mercaptobenzothiazole to amine should also not be higher than 1. The ratio preferably chosen is 1:4. An excess of amine has no disadvantageous influence on the process. The catalysts for use according to the invention may be present in a molar ratio of 1.75-2.521, preferably 2:1, based on the amount of sulphur dioxide present. Because the catalysts are salts of which the anion is related to an acid weaker than sulphurous acid, or compounds which react with sulphur dioxide, the hydrogen sulphite of alkali metal, alkaline earth metal or subgroup metal will be produced of course in the reaction mixture. It should be present in at least equimolar quantities, based on the amount of 2-mercaptobenzothiazole used.

The reaction may be carried out at the autogenous pressure corresponding to the reaction temperature or at 3 4 I elevated pressures in the region of 1 to 50 excess atmostained in 206 g.=222 ml. of a 30% by weight aqueous pheres, preferably 5 to 12 excess atmospheres and particusolution into which 64 g. '(1 mol) of sulphur dioxide have larly 7 to 9 excess atmospheres. The reaction temperabeen introduced are stirred for 3 hours in a stainless steel tures may vary within a wide range. Temperatures of beautoclave of 700 ml. capacity equipped with stirrer, at a tween 80 C. and 240 0., preferably between 160 C. 5 temperature of 160 and a pressure of 7-9' excess atmosand 180 C., are generally employed. pheres. After cooling to room temperature, the pressure Whereas it is explicitly stated in the publication referred in the autoclave is released (residual pressure less than to above that a reaction of 2-mercaptobenzothiazole with 1 excess atmosphere) and the reaction mixture is resecondaary amines does not take place, it has surprisingly moved by suction. The crude Z-methylaminobenzothiazole been found that in the process according to the inven- 10 which is present as a solid constituent is washed with hot tion even secondary amines can be reacted. 20% aqueous sodium hydroxide solution and with cold Working up of the reaction mixtures is carried out water, the dark-colored crude product being purified to by the conventional methods. give a beige-colored product. 78-80 g.'=95-98% of the The benzothiazoles obtainable by the process, which theory of 2-methylaminobenzothiazole (M.P.: 137-139), have an amine function in the 2-position, serve as interbased on the amount of Z-mercaptobenzothiazole put into mediate products for the production of plant-protective the process, are obtained. agents and may also be used directly as such. EXAMPLE 4 The temperatures quoted in the following examples are given i degrees i d The continuous product1on of Z-methylammobenzothiazole by reacting 40-50% 'by weight aqueous solutions EXAMPLE 1 (FOR COMPARISON) of 2-mercaptobenzothiazole in the form of its sodium salt 83.5 g. (0.5 mol) of 2-mercaptobenzothiazo1e (M.P.: and methylamine ill the form of a 30% y Weight aqueous 173-l78) and 62 g. (2.0 mols) of methylamine in 206 solution in the presence of sulphur dioxide in the molar g.'=222 ml. of a 30% by weight aqueous solution into ratio of 1:4:2 is carried out in three laboratory pressure which 64 g. (1 mol) of sulphur dioxide have been introvessels connected in series. These vessels are equipped duced are reacted in a stainless steel autoclave of 700 ml. With mechanical stirrers and are free from packing capacity equipped with stirrer at a temperature of 160 glands. They are products of the engineering company and a pressure of 7-9 excess atmospheres. The effect of SFS, Zurich, Switzerland. (These pieces of apparatus have varying the reaction time on the yield of 2-methylaminodouble-walled, heatable glass pressure containers 900 ml. benzothiazole (M.P.: 136-137) is summarised in Table in capacity which are designed for a pressure of 12 excess 1. The percentages refer to the amount of 2-mercaptoatmospheres at 200 C.; internal diameter 8.0 cm.; length benzothiazole put into the process. of stirrer blade 5.0 cm.; annular flow breaker; stirrer TABLEI free from packing glands and operated by magnetic coupling; infinitely variable differential gearing.) The Rwqtwn 2'methylammbenmhmmle solutions are fed into the apparatus by means of a time, Experiment number hours Grams Percent separately controlled two-headed pump. The effects of 1 26 32 varying the temperature and residence time on the con- 3 2% 23 version and yield is summarized in Table 3. 23 25 TABLE 3 6 56 68 10 65 80 Time of Reaction Percent 24 75 91 Experiments stay, tempera- Duration number hours ture, C. hours Conversion Yield XA 160 10 s9 89 E MPLE 2 165 12 92 92 83.5 g. (0.5 mol) of Z-mercaptobenzothiazole, if de- $8 13 3g 3g sired with the addition of equimolar quantities of oxides, 180 10 94 94 hyroxides or salts of acids weaker than sulphurous acid g 8% g:

of alkali metals, alkaline earth metals or sub-group metals 1 Mt t t h f m h t t fth 81 8. 1115 men 0 8 equi Hum 0! 01115, 8. 1115 men 0 e dlssolved or suspenfiled m 9 of Water: and 62 (2 equilibrium being determined by a time/conversion curve under intermols) of methylamine contained in 206 g.=222 ml. of a mittentoperafion- 30% aqueous solution into which 64 g. (1 mol) of sulphur dioxide have been introduced are reacted in a stainless EXAMPLE 5 steel autoclave of 700 ml. capacity equipped with stirrer 83.5 g. (0.5 mol) of the sodium salt of Z-mercaptoat a temperature of 160 C. and a pressure of 7-9 excess benzothiazole in 153 ml. of a 43% by weight aqueous atmospheres for 3.5 hours. The influence of the addition solution are reacted with 2 mols of a secondary amine in of salt on the yield of 2-methylaminobenzothiazole comthe presence of 64 g. (1 mol) of sulphur dioxide at 160 pared with the yield obtained in an experiment carried out C. for 3 hours in a stainless steel autoclave of 700 ml.

without salt is summarized in Table 2. capacity equipped with stirrer. The nature of the second- TABLE 2 Addition of salt Yield Experiment umber Grams Mol Type Grams Percent 0 0 49 12 0.5 Lithium hydroxide 20 0.5 Sodium hydr 'de 75 92 41 0. 76 93 27 5 76 93 2s 5 74 10 0. Magnesium oxide 60 73 19 0. Calcium hydroxide 65 79 83 0.25 Bis-mercaptobenzothiazolyl zinc salt;-- 71 86 EXAMPLE 3 ary amine, the yield of Z-dialkylamino-benzothiazole and 945 (05 mol) of the sodium Salt f 2 the result of analysis of the compounds, which are all new benzothiazole contained in 153 ml. of a 43% by weight With the exception of the dimethyl compound, are sumaqueous solution, and 62 g. (2 mols) of methylamine con- 75 marized in Table 4.

TABLE 4 Yield Molet'f Calculated, percent Found, percent Experiment Secondary M.P., Molecular ular number amine Grams Grams Percent C. formula weight C H N S C H N S 1-.- 90 54 61 85-87 CwHioNzS 178 60.6 5.6 15.7 17.9 60. 1 5.7 15.6 17. 8 2-..- 146 4 4 82-86 CuHuNaS 206 64.1 6.8 13.6 15.5 63.7 6.4 14.1 15. 8 3.... 142 30 29 89-91 CnHxzNzS 204 64.7 5.9 13.7 15.7 64.5 5. 9 13.7 15. 9 4... 170 24 22 84-88 CrzHuNzS 218 66.0 6.4 12.8 14.7 65.7 6.3 12.7 15.8 5- Hexamethylene imjne.-. 188 14 12 123-128 C1aHmNzS 232 67. 2 6. 9 12. 1 13. 8 68. 1 7. 1 11. 13. 8 6- Morpholine 174 52 47 123 CnHmNzOS 220 60. 0 5. 4 12.7 14. 60. 4 5. 8 12. 8 14.0 7- N-methylpiperazine 200 22 19 81-84 CmHwNaS 233 61.8 6.4 18.0 13.7 61.7 6.6 18.3 13.6

EXAMPLE 6 monia, pyrolidine, piperidine, hexamethylene imine, mor- 83.5 g. (0.5 mol) of Z-mercaptobenzothiazole (HMBT) suspended in 130 ml. of water or 94.5 g. (0.5 mol) of its sodium salt contained in 153 m1. of a 43% by weight aqueous solution, and 68 g. (4 mols) of ammonia contained in 276 g.=302 m1. of a 22.5% by weight aqueous solution into which 64 g. (1 mol) of sulphur dioxide have been introduced are stirred for 3 hours and 6 hours, respectively, in a stainless steel autoclave of 700 ml. capacity equipped with stirred, at a temperature of 160 C. and a pressure of 9-13 excess atmospheres. After cooling to room temperature, the residual pressure (less than 1 excess atmosphere) is released and the reaction mixture is removed by suction. The crude Z-aminobenzothiazole obtained as solid constituent is Washed with hot 20% sodium hydroxide solution and with cold water, the darkcolored crude product being purified to give a beige product (M.P.: 125128). The effect of the presence of the alkali metal and of varying the reaction time on the yield is summarized in Table 5.

1. Process for preparing Z-aminobenzothiazole and its N-al-kyl substitution products which comprises reacting Z-mercaptobenzothiazole in an aqueous medium with at least the stoichiometrically required quantity of a compound selected from the group consisting of ampholine, N-methylpiperazine and amines of the formula wherein R is C alkyl and R is hydrogen or C alkyl,

and with at least the stoichiometrically required quantity of sulphur dioxide in the presence of a catalyst selected from the group of an alkali metal, alkaline earth metal, and a metal of the first or second sub-group of the periodic system in the form of its oxides, hydroxides or salt of acids which are weaker than sulphurous acid, in the temperature range of C. to 240 C. at elevated pressure.

2. Process of claim 1 wherein ammonia or methylamine is used.

3. Process of claim 1 wherein the salts of acids which are weaker than sulphurous acid are salts of lower ali phatic carboxylic acids which have 1 to 4 carbon atoms, carbonic acid or Z-mercaptobenzothiazole.

4. Process of claim 1 carried out at 5 to 12 excess atmospheres.

5. Process of claim 1 carried out at to 180 C.

6. Process of claim 1 carried out continuously.

, References Cited Ubaldin et al.: Chemical Abstracts, 41:960-1 (1947).

RICHARD J. GALLAGHER, Primary Examiner US. Cl. X.R. 

